Efficacy and Tolerability Study in Severe Chronic Obstructive Pulmonary Disease (COPD) Patients

Phase 4

Completed

Conditions: Chronic Obstructive Pulmonary Disease (COPD)

Interventions: Drug: theophylline SR

Registration Number: NCT01415518

Lead Sponsor: AstraZeneca

Brief Summary: Efficacy and tolerability study in severe chronic obstructive pulmonary disease (COPD) patients.

Detailed Description: Efficacy and tolerability study of Symbicort Turbuhaler (160/4.5µg/inhalation,2inhalations twice daily) added to Atrovent (20µg/inhalation, 2 inhalations 4 times daily) + theophylline SR(0.1g/tablet, 1 tablet p.o. twice daily) compared with Atrovent + theophylline SR in severe COPD patients.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 581

Inclusion Criteria

Signed and dated informed consent
Men or women patients ≥ 40 years of age
Diagnosis of COPD with symptoms for more than 2 years and there is a history of at least one COPD exacerbation requiring a course of oral steroids and/or antibiotics within 1-12 months before Visit 2
Forced Expiratory Volume in 1 second (FEV1) ≤50% of predicted normal value, pre-bronchodilator and Forced Expiratory Volume in 1 second (FEV1) / Forced Vital Capacity (FVC) < 70%, pre-bronchodilator
Total symptom score of 2 or more per day for at least half of run-in period (breathing, cough and sputum scores from the diary card) and complete morning recordings of Digital Peak Flow Meter data at least 7 out of the last 10 days of the run-in period

Exclusion Criteria

A history of asthma and seasonal allergic rhinitis before 40 years of age
Patients who have experienced exacerbation of COPD requiring hospitalisation and /or emergency room treatment and/or a course of oral steroids and/or intravenous corticosteroids and/or antibiotics within 4 weeks prior to Visit 2 and/or during run-in period
Patients with relevant cardiovascular disorder judged by the investigator
Patients with glaucoma, prostatic hyperplasia or bladder-neck obstruction judged by the investigator
Women who are pregnant, breast-feeding or of child-bearing potential judged by the investigator

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	theophylline SR	budesonide/formoterol (Symbicort Turbuhaler 160/4.5µg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 µg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
2	theophylline SR	ipratropium (AtroventTM 20 µg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)

Primary Outcome Measures

Name	Time	Method
Pre-dose FEV1	Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug	Ratio of pre-dose FEV1 (Forced Expiratory Volume in 1 second) in treatment period to baseline value

Secondary Outcome Measures

Name	Time	Method
Post-dose IC at 60 Minutes	Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)	Ratio of post-dose IC at 60 minutes to baseline
Post-dose PEF in First Week of Treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurments measured at 5 minutes after inhalation of study drug in the first week of treatment	Change in post-dose morning PEF at 5 minutes from run-in period to first week of treatment
Use of Reliever Medication During Day in the Last Week on Treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatment	Change in the number of inhalations of reliever medication during day from run-in to the last week on treatment
Use of Reliever Medication During Day in the First Week on Treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the first week on treatment	Change in the number of inhalations of reliever medication during day from run-in to the first week on treatment
Use of Reliever Medication During Day in the Whole Treatment Period	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period (12 weeks)	Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period
Post-dose FEV1 at 60 Minutes	Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)	Ratio of post-dose FEV1 at 60 minutes to baseline value
Pre-dose PEF in Whole Treatment Period	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in whole treatment period (12 weeks)	Change in pre-dose morning PEF from run-in period to whole treatment period
Post-dose PEF in Whole Treatment Period	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in whole treatment period (12 weeks)	Change in post-dose morning PEF at 5 minutes from run-period to whole treatment period
COPD Symptoms - Cough	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks)	Change in cough symptom score (from 0 (none) to 4 (almost constant)) from run-in period
COPD Symptoms Sputum	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks)	Change in sputum symptom score (from 0 (none) to 4 (severe)) from run-in period
Pre-dose FVC	Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)	Ratio of pre-dose FVC (Forced Vital Capacity) to baseline
Pre-dose IC	Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)	Ratio of pre-dose IC (Inspiratory Capacity) to baseline
Pre-dose PEF in Last Week of Treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the last week of treatment	Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to last week of treatment
Post-dose PEF in Last Week of Treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the last week of treatment	Change in post-dose morning PEF at 5 minutes from run-period to last week of treatment
Use of Reliever Medication During Night in the First Week on Treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the first week on treatment	change in the number of inhalations of reliever medication during day from run-in to the first week on treatment
Change in COPD Symptoms - Breathing	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks)	Change in breathing symptom score (from 0 (none) to 4 (severe)) from run-in period
Post-dose FEV1 at 5 Minutes	Baseline (-2 weeks) and mean in treatment period (1, 6, 12 weeks) measured at 5 minutes after inhalation of study drug	Ratio of post-dose FEV1 at 5 minutes to baseline value
Post-dose FVC at 5 Minutes	Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 5 minutes after inhalation of study drug at weeks 0, 1, 6, 12)	Ratio of post-dose FVC at 5 minutes to baseline
Post-dose FVC at 60 Minutes	Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)	Ratio of post-dose FVC at 60 minutes to baseline
COPD Exacerbations	Whole treatment period (12 weeks)	Severe exacerbations requiring systemic steroids (oral ≥3 days or parenteral) or hospitalisation or emergency room treatment due to worsening of COPD symptoms
Use of Reliever Medication During Night in the Last Week on Treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the last week on treatment	Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period
Use of Reliever Medication During Night in the Whole Treatment Period	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the whole treatment period (12 weeks)	Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period
Pre-dose PEF in First Week of Treatment	Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurments measured before inhalation of study drug in the first week of treatment	Change in pre-dose morning PEF from run-in period to first week of treatment